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"identified four sites (Ser-124, Thr-308, Thr-450, and Ser-473) on Akt1 that are phosphorylated in vivo. Thr-308 and Ser-473 are inducibly phosphorylated after treatment of cells with extracellular stimuli, whereas Ser-124 and Thr-450 appear to be basally phosphorylated The third mechanism by which 3'-phosphorylated phosphoinositides regulate Akt activity is by controlling the accessibility of Akt as a substrate for PDKs. In in vitro reconstitution assays, the binding of PI3,4,5P to the Akt PH domain is required for PDK-1 to phosphorylate Akt In addition, PDK-1 complexed with either a fragment of PRK2, PRK2, or a PRK2-related peptide may be regulated by increased phospholipid concentrations"

"Fig. 1. Insulin-like growth factor 1 (IGF-1)-mediated signaling pathways relevant to hypertrophy. Binding of IGF-1 activates the IGF-1 receptor (purple), which then recruits insulin-receptor substrate (IRS-1). This leads to the activation of two signaling pathways: the Ras-Raf-MEK-ERK pathway and the phosphatidylinositol 3-kinase (PI3K)- Akt pathway. The PI3K-Akt pathway recapitulates hypertrophy caused by IGF-1 stimulation. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] (orange). Signaling molecules that have been shown to have a negative effect on hypertrophy are colored red, and proteins whose activation induces hypertrophy are shown in green. Proteins that have not been assayed for their role in hypertrophy are shown in blue. Abbreviations: eIF-2B, eukaryotic translation initiation factor 2B; ERK, extracellular-signal-regulated kinase; GSK3b, glycogen-synthase kinase 3b; mTOR, mammalian target of rapamycin; p70S6K, p70 S6 kinase; PDK, phosphoinositide-dependent protein kinase; PtdIns(3,4)P2, phosphatidylinositol (3,4)-bisphosphate; PtdIns(4,5)P2, phosphatidylinositol (4,5)-bisphosphate; PHAS-1, phosphorylated heat- and acid-stable protein 1; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homologous on chromosome 10; SHIP2, SH2-domain-containing inositol phosphatase; Tsc1/2, tuberous sclerosis complex 1 and 2. Modified from Ref. [87]. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, PtdIns(3,4,5)P3 [22] (Fig. 1). Akt1 activity depends on phosphorylation at two sites: Ser473 and Thr309 [29]."

"In vivo 32P labeling and mutagenesis demonstrated that m/p-PKBalpha activity was due to phosphorylation on Thr308 and Ser473, that are normally induced on PKB following stimulation of the cells with insulin or insulin-like growth factor-1 (IGF-1).... Following activation the kinase detached from the membrane and translocated to the nucleus."

"mTORC2 can be activated by PI3K directly and phosphorylates Akt at S473, which together with phosphorylation at T308 results in the full activation of Akt [12,13]."

"Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently."

"Fig. 1. Insulin-like growth factor 1 (IGF-1)-mediated signaling pathways relevant to hypertrophy. Binding of IGF-1 activates the IGF-1 receptor (purple), which then recruits insulin-receptor substrate (IRS-1). This leads to the activation of two signaling pathways: the Ras-Raf-MEK-ERK pathway and the phosphatidylinositol 3-kinase (PI3K)- Akt pathway. The PI3K-Akt pathway recapitulates hypertrophy caused by IGF-1 stimulation. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] (orange). Signaling molecules that have been shown to have a negative effect on hypertrophy are colored red, and proteins whose activation induces hypertrophy are shown in green. Proteins that have not been assayed for their role in hypertrophy are shown in blue. Abbreviations: eIF-2B, eukaryotic translation initiation factor 2B; ERK, extracellular-signal-regulated kinase; GSK3b, glycogen-synthase kinase 3b; mTOR, mammalian target of rapamycin; p70S6K, p70 S6 kinase; PDK, phosphoinositide-dependent protein kinase; PtdIns(3,4)P2, phosphatidylinositol (3,4)-bisphosphate; PtdIns(4,5)P2, phosphatidylinositol (4,5)-bisphosphate; PHAS-1, phosphorylated heat- and acid-stable protein 1; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homologous on chromosome 10; SHIP2, SH2-domain-containing inositol phosphatase; Tsc1/2, tuberous sclerosis complex 1 and 2. Modified from Ref. [87]. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, PtdIns(3,4,5)P3 [22] (Fig. 1). Akt1 activity depends on phosphorylation at two sites: Ser473 and Thr309 [29]."

"Upon stimulation with insulin, AKT is recruited to cellular membranes by binding of its amino terminal pleckstrin (PH) domain to membrane bound phosphatidylinositol 3,4,5, trisphosphate (PIP3) [3]. The membrane bound form of AKT then becomes phosphorylated on two regulatory residues, a threonine within the activation loop (Thr308 in AKT1,Thr309 in AKT2, Thr305 in AKT3) and a serine in the C-terminus of the enzyme (Ser473 in AKT1,Ser474 in AKT2, Ser472 in AKT3), and both phosphorylations are considered to be required for AKT to reach maximum kinase activity [1]. The kinase responsible for phosphorylation of Thr308/309/305 has been identified as phosphoinositide-dependent kinase 1 (PDK1) [3]."

"three isoforms, AKT1 (PKBalpha), AKT2 (PKBbeta) and AKT3 (PKBgamma) they all contain a central kinase domain with an activation-loop phosphorylation site, Thr308, and a conserved, regulatory C-terminal phosphorylation site, Ser473"

"Phosphorylation at Ser473 in the hydrophobic motif, along with Thr308 in its activation loop, is considered necessary for Akt function."

"Thrombin induces the activation of platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at threonine 308 and serine 473."

"After PIP3 binding, Akt1 is activated by phosphorylation on two critical residues, namely threonine %308 (T308) and serine 473 (S473); similar activation residues (S472 and S474, %respectively) are highly conserved in Akt2 and Akt3 Phosphoinositol-3-phosphate (PIP3) is a product of phosphoinositol 3-kinase enzymatic activity and has been shown to be a prerequisite lipid modulator of Akt activity Akt activity can be regulated by the PTEN tumour suppressor gene, which negatively regulates PIP3 levels PIP3 has been described as a downstream component of a wide range of receptors, including the c-Met receptor [5], the epidermal growth factor receptor family [6], fibroblast growth factor receptor [7], insulin growth factor receptor [8] and platelet-derived growth factor receptor"

"Conversely, the H157 cells, which showed decreased T308 phosphorylation with serum deprivation, exhibited less kinase activity in low serum."

"Akt becomes activated upon phosphorylation of Ser473 and Thr308. In the absence of insulin, dexamethasone reduced Ser473 phosphorylation by 33% (P < 0.05 vs. no treatment, n = 3)."

"Akt becomes activated upon phosphorylation of Ser473 and Thr308. In the absence of insulin, dexamethasone reduced Ser473 phosphorylation by 33% (P < 0.05 vs. no treatment, n = 3)."

"In vivo 32P labeling and mutagenesis demonstrated that m/p-PKBalpha activity was due to phosphorylation on Thr308 and Ser473, that are normally induced on PKB following stimulation of the cells with insulin or insulin-like growth factor-1 (IGF-1).... Following activation the kinase detached from the membrane and translocated to the nucleus."

"Thrombin induces the activation of platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at threonine 308 and serine 473. "

"Upon stimulation with insulin, AKT is recruited to cellular membranes by binding of its amino terminal pleckstrin (PH) domain to membrane bound phosphatidylinositol 3,4,5, trisphosphate (PIP3) [3]. The membrane bound form of AKT then becomes phosphorylated on two regulatory residues, a threonine within the activation loop (Thr308 in AKT1,Thr309 in AKT2, Thr305 in AKT3) and a serine in the C-terminus of the enzyme (Ser473 in AKT1,Ser474 in AKT2, Ser472 in AKT3), and both phosphorylations are considered to be required for AKT to reach maximum kinase activity [1]. The kinase responsible for phosphorylation of Thr308/309/305 has been identified as phosphoinositide-dependent kinase 1 (PDK1) [3]."

"All three isoforms (PKBalpha, PKBbeta and PKBgamma) were phosphorylated at similar rates and activated to similar extents by 3-phosphoinositide-dependent protein kinase-1 (PDK1)"

"IL-4 induces PI-3K activity, as shown by Western blotting analysis, demonstrating the specific phosphorylation of PKB, a downstream substrate of PI-3K, at residues Ser473 and Thr308."

"All three isoforms (PKBalpha, PKBbeta and PKBgamma) were phosphorylated at similar rates and activated to similar extents by 3-phosphoinositide-dependent protein kinase-1 (PDK1)"

"Conversely, the H157 cells, which showed decreased T308 phosphorylation with serum deprivation, exhibited less kinase activity in low serum."

"three isoforms, AKT1 (PKBalpha), AKT2 (PKBbeta) and AKT3 (PKBgamma) they all contain a central kinase domain with an activation-loop phosphorylation site, Thr308, and a conserved, regulatory C-terminal phosphorylation site, Ser473"

"In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways."

"Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently."

"Stimulation of platelets with a PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin resulted in Thr308 and Ser473 phosphorylation of Akt, which results in its activation."

"After PIP3 binding, Akt1 is activated by phosphorylation on two critical residues, namely threonine %308 (T308) and serine 473 (S473); similar activation residues (S472 and S474, %respectively) are highly conserved in Akt2 and Akt3 Phosphoinositol-3-phosphate (PIP3) is a product of phosphoinositol 3-kinase enzymatic activity and has been shown to be a prerequisite lipid modulator of Akt activity Akt activity can be regulated by the PTEN tumour suppressor gene, which negatively regulates PIP3 levels PIP3 has been described as a downstream component of a wide range of receptors, including the c-Met receptor [5], the epidermal growth factor receptor family [6], fibroblast growth factor receptor [7], insulin growth factor receptor [8] and platelet-derived growth factor receptor"

"Phosphorylation at Ser473 in the hydrophobic motif, along with Thr308 in its activation loop, is considered necessary for Akt function."

"identified four sites (Ser-124, Thr-308, Thr-450, and Ser-473) on Akt1 that are phosphorylated in vivo. Thr-308 and Ser-473 are inducibly phosphorylated after treatment of cells with extracellular stimuli, whereas Ser-124 and Thr-450 appear to be basally phosphorylated The third mechanism by which 3'-phosphorylated phosphoinositides regulate Akt activity is by controlling the accessibility of Akt as a substrate for PDKs. In in vitro reconstitution assays, the binding of PI3,4,5P to the Akt PH domain is required for PDK-1 to phosphorylate Akt In addition, PDK-1 complexed with either a fragment of PRK2, PRK2, or a PRK2-related peptide may be regulated by increased phospholipid concentrations"

"Stimulation of platelets with a PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin resulted in Thr308 and Ser473 phosphorylation of Akt, which results in its activation."